Biomedical subjects

L J Degroot

Publications and source records attributed to L J Degroot.

36 records · Page 2Linked to original sources

PubMed1975

Immunologic aspects of human thyroid cancer. Humoral and cell-mediated immunity, and a trial of immunotherapy.

Immunologic studies were performed on 16 patients with thyroid cancer. Circulating leukocyte counts increased, parallel to development of the terminal stage of disease, but total lymphocytes decreased. Serum immunoglobulin and complement were high, even though almost all patients showed negative antithyroid antibodies. Delayed skin hypersensitivity to bacterial and viral antigens and lymphocyte responsivity to PHA were not impaired at the initial stage of disease, but were impaired in terminal illness. Cell-mediated immunity (CMI) to tumor antigens(s) was measured using the assays of lymphotoxin, migration inhibition factor, and peripheral leukocyte migration inhibition. A few patients showed significant response to tumor antigen, but not to homogenates of Graves' thyroid gland. Active immunotherapy was applied to three patients. Two patients, who were in the terminal stage of illness, could not develop generalized CMI; immunization did not alter the patients' rapid downhill course. One patient developed in vitro evidence of CMI against cancer tissue antigens, associated with decrease in tumor size. Four months after immunization, CMI was impaired in autologous plasma culture, but not in cultures in allogenic normal plasma.

Adenocarcinoma↗

PubMed1975

Insoluble particulate antigen(s) in cell-mediated immunity of autoimmune thyroid disease.

Cell-mediated immunity (CMI) in patients with Grave's disease, chronic thyroiditis, and primary hypothyroidism was observed by assay of lymphocyte-mediated cytotoxicity (LMC) and leukocyte migration inhibition (LMC). Lymphocyte responsivity to phytohemagglutinin (PHA) is normal in these disease. In the LMC assay, lymphocytes of patients in each category responded to the antigens of thyroid homogenates, but not purified human thyroglobulin. Cytotoxicity is least in Graves disease and most obvious in primary hypothyroidism. In the LMI assay, patients lymphocytes responded to thyroid microsomal--mitochondrial antigens, but not to thyroid cell sap. Lymphocytes of Graves disease patients also responded to liver microsomal mitochondrial antigens. The particulate antigens lost activity when solubilized by ultrasonication or KCL extraction. There is no correlation between the PHA responsivity of lymphocytes and thyroid function, or between CMI and serum antithyroid antibodies or thyroid size. Treated and untreated patients had similar evidence of CMI. These data indicate that function of thymus-derived lymphocyte in vitro is not disturbed in autommune thyroid disease and that CMI against thyroid antigens can be demonstrated by assay of LMC and LMI. Insoluble particulate antigens appear more important than soluble antigens in CMI. LMC, resumably induced by soluble cytotoxic factor, "lymphotoxin," may play an important role in the progress of the autoimmune thyroid disease to hypothyroidism.

Antigens↗

PubMed1975

Differentiation of two abnormalities in thyroid peroxidase causing organification defect and goitrous hypothyroidism.

Clinical and laboratory evaluations are reported on two patients with congenital goiter and hypothyroidism due to iodide organification defect. In one patient, a 31-year-old white male with severe mental retardation, administration of perchlorate caused discharge of 69% of the radioiodine accumulated in the thyroid gland. Thyroid tissue had negligible peroxidase activity in the tyrosine-iodinase, triliodide, and guaiacol assays. Preincubation of subcellular fractions with hematin restored activity. The restored enzyme was labile to high concentrations of H2O2 (5.6times 10-4 h2o2 produced inhibition in the triiodide assay). Heating of the enzyme for 5 min at 46 degrees C produced 50% inactivation, while higher temperatures were required to half-inactivate normal peroxidases. This case represents a second example of the "peroxidase apoenzyme-prosthetic group defect" causing congenital goiter. The second patient, an example of the "deficient peroxidase defect," was a 10-yr-old girl with 35% discharge of thyroidal radioiodine by perchlorate. Peroxidase activity in the goiter tissue was quantitatively decreased (10%-20% of normal values) but kinetically normal with respect to apparent Km for H2O2. Hematin had little effect on the enzyme. Peroxidase activity had abnormal subcellular distribution, since pellets sedimenting between 39,000 and 105,000 g contained most of the activity. Normal thyroglobulin was observed in the thyroid gland of the patient. Two distinct defects of the peroxidase system can produce congenital goiter by limiting organification of iodide.

Adult↗

PubMed1974

Nuclear triiodothyronine-binding protein: partial characterization and binding to chromatin.

Nuclei were prepared by sucrose sedimentation of liver homogenates from rats given (125)I-labeled triiodothyronine in vivo. The nuclear extract obtained by treatment of the nuclear pellet with 0.4 M KCl contains the [(125)I]triiodothyronine that had been injected in vivo bound to protein(s). The triiodothyronine bound to nuclear protein(s) in vivo does not readily exchange with triiodothyronine added to the extract in vitro. This triiodothyronine.nuclear extract complex retains triiodothyronine during dialysis or exposure to anion exchange resin and migrates as a broad band on agarose-gel electrophoresis. It is rapidly destroyed by Pronase, by 8 M urea, and by p-chloromercuribenzoic acid, but not by RNase or by DNase. It is also susceptible to thermal inactivation at 37 degrees , possibly through changes in the affinity of triiodothyronine to the nuclear binding protein(s), since the bound triiodothyronine becomes more readily dialyzable, is absorbed by an anion exchange resin, but retains its characteristic mobility on electrophoresis. The triiodothyronine.nuclear extract complex formed in vivo binds to crude liver chromatin in vitro at low salt concentration, but can be completely extracted again at KCl concentrations greater than 0.2 M.

Animals↗

PubMed1973